CZ23404U1 - Dialyzing and substitution solution - Google Patents

Abstract

Dialysis and substitution fluid, designed for elimination techniques with citrate anticoagulation in the intensive care setting, wherein the fluid comprises 125 to 135 mmol/I Na, 0 to 4 mmol/l K, 0.8 to 1.8 mmol/I Mg, 110 to 125 mmol/I Cl, 0.8 to 1.2 mmol/I P, 15 to 25 mmol/I Na-lactate and 5.0 to 6.0 mmol/I glucose, where osmolality is in the range of 270 to 285 mOsm/kg. The fluid can comprise 130 mmol/l Na, 2 memol/l K, 1.5 mmol/l Mg, 116 mmol/l Cl, 1.0 mmol/l P, 18 mmol/l Na-lactate and 5.6 mmol/l glucose, where osmolality of the fluid is 274 mOsm/kg. Single chamber bag generally applicable with citrate anticoagulation that contains dialysis and substitution fluid as described above.

Description

Dialysis and substitution solution

The Industrial Property Office does not ascertain in the registration procedure whether the subject of the utility model meets the conditions of eligibility for protection pursuant to Section 1 of Act no. No. 478/1992 Coll.

Dialysis and substitution solution

Technical field

The subject of the technical solution is a dialysis and substitution solution intended for performing elimination methods in intensive care in which citrate anticoagulation is applied.

BACKGROUND OF THE INVENTION

Critically ill patients hospitalized in intensive care units require, in 3 to 25% of cases depending on the nature of the unit, the application of some of the methods of continuous extracorporeal blood purification (CRRT). Blood flow by extracorporeal circulation requires anticoagulant therapy, otherwise blood elements are taken up and the coagulation cascade is activated. This may result in a decrease in platelets, loss of coagulation factors, potentiation of systemic inflammation and a consequent risk of bleeding. If we try to reduce these phenomena by anticoagulation, such as heparin, in difficult titration the critically ill patient may bleed from various sources (wounds, gastrointestinal tract, invasive inputs, CNS ...) (Kleger GR, Fassler E: Can circuit lifetime be a Int J Artif Organs 2010, 33: 139-146; Betjes MG, van Oosterom D, van Agteren M, van de Wetering J: Regional citrate versus heparin anticoagulation during venovenous haemofiltration in patients at low risk for bleeding: simulated hemophilic survival but significantly less bleeding (J Nephrol. 2007; 20: 6028). Citrate anticoagulation has proven to be the best and safest possible solution. In developed healthcare systems, a growing proportion of patients requiring CRRT are required for citrate anticoagulation (Oudemans van Straaten HM, Bellomo R, Kellum JA: Clinical review: Anticoagulation for continuous renal replacement therapy - Heparin or Citrate? Crit Care 2011, 15: R202; Oudemans-van Straaten HM, Wester JP, de Pont AC, Schetz MR: Anticoagulation strategies in continuous renal replacement therapy: intensive care med 2006, 32: 188-202; Monchi M, Berghmans D, Ledoux D , et al: Citrate vs. heparin for anticoagulation in continuous venovenous haemofiltration: a prospective randomized study Intensive Care Med 2005, 30: 260-265, Oudemans-van Straaten HM, Bosman RJ, Koopmans M, et al: Citrate anticoagulation for continuous Crit Care Med 2009, 37: 545-552; Hetzel GR, Schmitz M, Wissing H, et al: Regional citrate versus systemic heparin for anticoagulation in critically ill patients on continuous venove nous haemofiltration: a prospective randomized multicenter trial. Nephrol Dial Transplant 2011, 26: 232-239; Package M, Waldauf P, Plašil P, Páchl J: Prostacyclin versus citrate in continuous haemodiafiltration: an observational study in patients with high risk of bleeding. Blood Purif 2005, 23: 325-329). The citrate regimen requires the application of commercially available citrate solutions and the application of their dialysis and replacement solutions.

In the past, the composition of solutions intended for continuous elimination methods (CRRT) in intensive care was based on the composition of peritoneal dialysis solutions. The solutions require an active approach of the intensives, control of the patient's homeostasis and corrective interventions into their ionic and acid-base composition. These interventions in the composition are even more necessary when citrate anticoagulation is used, which fundamentally affects the acid-base balance and iontogram. Table 1 shows examples of commercially available solutions. Their content is derived from the plasma composition and the first 3 solutions (Baxter E2, Medisol K2 and Medisol BiO) are intended primarily for heparin anticoagulation. The solutions on the right side of Table 1 (Fresenius CiCa K2, GML Citralysate K2, PrismOcal) are intended for citrate anticoagulation. It is evident that a reduction in the amount of sodium is required, since citrate is infused to the beginning of the extracorporeal device mostly as the sodium salt. This poses a risk of hypematremia, particularly when using trisodium citrate, since about 40 to 50% of the infused amounts are eliminated on the filter in various configurations and 50 to 60% enter the patient (Mariano F, Morselli M, Bergamo D, et al: Blood and ultrafiltrate dosage of citrate as a useful and routine tool during continuous venous haemodiafiltration in septic shock patients Nephrol Dial Transplant 1-7, doi: 10.1093 / ndt / gfrl06, published online 8.3.2011; Balik M, Zakharchenko M, Otahal M, et al:

- 1 GB 23404 U1

Quantification of systemic dose of substrates for intermediate metabolism during citrate anticoagulation of continous renal replacement therapy. Blood Purif 2011, in print; Package M, Zakharchenko M, January P, et al: Bioenergetic gain of citrate anticoagulated continuous haemodiafiltration - comparative study of two algorithms. J Crit Care 2011, under review).

Table 1: Overview of available CRRT dialysis / substitution solutions on the market. The price is approximate including VAT and distribution, refers to December 2011.

Composition in (mmol / 1) BaxterE2 Medisol K2 Medisol BiO Fresenius CiCa K2 GML Citralysate K2 PrismOcal * On 142 140 141 133 133 140 TO 1.5 2,0 - 2,0 2,0 - Ca 1.90 1.50 0.80 - - - Mg 0.75 0.75 1.00 0.75 0.75 0.5 Cl 108.8 106.5 103.8 116.5 116.5 106 P - - 0.80 - - - Na-lactate 40 40 - - - 3.0 hco ₃ - - - 40 20 May 20 May 32 glucose 5,05 6.0 6.7 5.6 5.6 - Acetate - - 4.2 - - Eight 300 296.0 298.3 278.0 282 Price (CZK / 5 1) 210 323 441 482 450 i don't find out.

* Prism0cal requires administration only with anticoagulant solution Prismocitrate 10/2 in predilution (Ingredients: citrate 10 mmol / l, citric acid 2.0 mmol / l, Na 140 mmol / l, Cl 106 mmol / l, Eight 254 mOsm / kg) .

Table 1 shows in the last column on the right the composition of Gambro-Hospal replacement solution, which requires a combination with isotonic low-concentrated citrate (about 12 mmol / l). This is less concentrated, but is infused in larger volumes. The disadvantage of low citrate concentration is imperfect anticoagulation with approximately half the filter survival compared to approximately ten times more concentrated triple sodium citrate (136 mmol / l) - see Palsson R, Niles JL: Regional citrate anticoagulation in continuous venous haemofiltration in critically ill patients with high Risk of bleeding. Kidney Int 1999, 55: 1991-7.

Even so, with the prior solutions listed in Table 1, it is necessary to maintain a certain minimum flow rate of these solutions by dialysis or to reduce the blood flow through the system to avoid hypematremia and alkalosis (see below). This is because citrate is dosed at the beginning of the blood set, which is proportional to blood flow and elimination on a filter that is proportional to the dialysis flow (see Oudemans van Straaten HM, Bellomo R, Kellum JA): Clinical review: Anticoagulation for continuous renal replacement therapy Crit Care 2011, 15: R202; Mariano F, Morselli M, Bergamo D, et al: Blood and ultrafiltrate dosage of citrate as a useful and routine tool during continuous venous haemodiafiltration in septic shock patients Nephrol Dial Transplant 1- 7, doi: 10.1093 / ndt / gfrl06, published online Mar 8, 2011, Package M, Zakharchenko M, Otahal M, et al: Quantification of systemic dose of substrates for intermediate metabolism during citrate anticoagulation of continous renal replacement therapy. 2011, in press;

Package M, Zakharchenko M, January P, et al: Bioenergetic gain of citrate anticoagulated continuous haemodiafiltration comparative study of two algorithms. J Crit Care 2011; Morgera S, Scholle C, Voss G, et al: Metabolic Complications during Regional Citrate Anticoagulation in Continuous Venovenous Hemodialysis: Single-Center Experience Nephron Clin Pract 2004, 97: 131-136; Morgera S, Haase M, and Ruckert M, et al: Regional Citrate Anticoagulation in Continuous Hemodialysis - Acid-Base and Electrolyte Balance at an Increased Dose of Dialysis. Nephron Clin Pract 2005, 101: 211-219; Morger S, Schneider M; Slowinski T, et al

-9 CZ 23404 Ul safe citrate anticoagulation protocol with variable treatment efficacy and excellent control of acid-base status. Crit Care Med 2009, 37: 2018-2024.

As major work has recently been published on the dose of dialysis / filtration, morbidity and mortality in critically ill patients (see RENAL Replacement Therapy Study Investigators, Bellomo R, Cass A, Cole L, et al: Intensity of continuous renal-replacement therapy in critically ill N Engl J Med 2009, 361: 1627-38; VA / NIH Acute Renal Failure Trial Network, Palevsky PM, Zhang JH, O'Connor TZ, et al: Intensity of Renal Support in Critically Ill Patients with Acute Kidney Injury. N Engl J Med 2008; 359: 7-20), a dosage of between 20 and 25 ml / kg.h is currently used rather than a higher dosage of about 35 ml / kg.h. This is also due to economic reasons. Therefore, at a dialysis dose of about 20 to 25 ml / kg.h, a relatively slow blood flow of between 90 to 110 ml / min is chosen in order not to lift the citrate dose into the circuit too much. However, this slow blood flow limits ultrafiltration in certain marginal situations (eg, patient's pulmonary edema, postdilution continuous haemofiltration - CVVH), since the amount of plasma fluid withdrawn on the filter per hour (ultrafiltration) should not exceed 20% of the blood flow through the filter per hour. When this happens, there is a critical increase in the hematocrit at the venous end of the filter, which increases the risk of clotting and loss of both the blood elements and the filter itself.

Citrate is metabolised to bicarbonate (three molecules of bicarbonate are formed from one citrate molecule), which can lead to metabolic alkalosis (see Oudemans van Straaten HM, Bellomo R, Kellum JA): Clinical review: Anticoagulation for continuous renal replacement therapy - heparin or citrate? Care 2011, 15: R202; Oudemans-van Straaten HM, JP Wester, de Pont AC, Schetz MR: Anticoagulation strategies in continuous renal replacement therapy: can be selected based on medication Care Med 2006, 32: 188-202). Therefore, in citrate anticoagulation solutions, the base content is reduced and citrate dosing is largely related to blood flow and elimination to dialysis flow (see above). If a bicarbonate buffer is used, the composition adjustments for citrate anticoagulation consist in a reduction of the amount of bicarbonate and / or bicarbonate. its replacement on the anionic side by chlorides.

In recent years, more physiological bicarbonate buffer has displaced lactate buffered solutions. Interestingly, there is no evidence that bicarbonate buffering is better for a patient than lactate. In addition, lactate is an excellent fuel for intermediate metabolism under stress conditions, sepsis and renal failure. Among others, his work demonstrates his significant doses during CRRT buffering (Bollmann MD, Revelly JP, Tappy L, et al: Effect of bicarbonate and lactate buffer on glucose and lactate metabolism during haemodiafiltration in patients with multiple organ silure, Intensive Care Med 2004, 30: 1103-1110; Left B, Mansart A, Montemont C, et al: Myocardial lactate deprivation associated with reduced cardiovascular performance, reduced myocardial energy, and early death in endotoxic shock Intensive Care Med 2007, 33: 495-502; Leverve X, Mustafa I. Novak I, et al: Lactate Metabolism in Acute Uremia (J Ren Nutr 2005, 15: 58-62). The main reason for bicarbonate is for clinicians to be prejudiced by the "lactate load" and some loss of lactate as a marker of anaerobic metabolism in shock states. However, bicarbonate is unstable in a cationic solution and requires a two-chamber bag that is more difficult to manufacture and store than a single-chamber bag with a stable Na-lactate buffered solution. A two-chamber bag requires a special seam to break both components before use or to deliver one component in a separate package. After mixing the two components, a final solution with limited stability is formed which must be used immediately. Single-chamber bags contain only stable solutions that have a longer expiration time than storage in the double-chamber.

In addition, it is necessary to discard calcium (calcium) from the bag so that it can be used both as a dialysis solution and at the same time as a pre-filtration (i.e. applicable before the filter) hemofiltration solution. This is due to regional calcium uptake by citrate, where exogenous calcium intake at the beginning of the circuit / filter means an increase in the citrate dose to neutralize it and thus a higher systemic citrate dose. Partial neutralization of citrate as it passes through the filter and blood set also results in shorter filter survival associated with clotting on the venous (distal) parts of the set (Package M, Zakharchenko M, Otahal M, et al: Quantification of systemic dose of substrates for intermediate metabolism during citrate anticoagulation of continous renal replacement therapy, Blood Purif 2011, in print; Package M, Zakharchenko M,

-3GB 23404 U1

January P, et al: Bioenergetic gain of citrate anticoagulated continuous haemodiafiltration - comparative study of two algorithms. J Crit Care 2011, under review).

However, citrate anticoagulation also appears to interfere with the metabolism of magnesium (magnesium), although the affinity for ionized magnesium is apparently lower than that of calcium. Magnesium levels in common solutions have been shown to be inadequate in the case of citrate anticoagulation and may lead to depletion of relatively low magnesium body stores within a few days (Zakharchenko M, Balik M, January P, et al: Citrate anticoagulated continuous haemodiafiltration: Focus on ionised magnesium Intensive Care Med 2011, 37, S336 (abstract). In addition to the elimination method itself, there are a number of other effects that reduce the body's magnesium stores (diuretics, intestinal losses), and the fact that extracellular magnesium does not reflect the state of the main body pool by intracellular plays a role. The effect of hypomagnesaemia on the incidence of arrhythmias and myopathies has been demonstrated (Soliman HM, Mercan D, Lobo SS, Melot C, Vincent JL: Development of ionized hypomagnesemia associated with higher mortality rates. Crit Care Med 2003; 31: 1082-1087).

The standard solutions do not contain phosphorus as it is expected to be excreted as part of renal insufficiency. In the case of CRRT in critically ill patients, however, renal replacement is indicated earlier than in classical dialysis and therefore phosphorus levels are lower. In the case of the continuous method, phosphorus must be paid very early. Failure to do so or lack of substitution may damage the patient with severe hypophosphatemia. This "omission" has already been partially addressed by Medisol Bio from Medites (see Table 1). Again, the negative impact of severe hypophosphatemia on the muscles, heart, nervous system and nutrition of patients has been demonstrated (Broman M, Carlsson O, Friberg H, Wieslander A, Godaly G: Phosphate-containing dialysis solution due to continuous renal replacement therapy. 2011; 55: 39-45; Demirjian S, Teo BW, Guzman JA, et al: Hypophosphatemia during continuous hemodialysis associated with prolonged respiratory failure in patients with acute kidney injury. Nephrol Dial Transplant 2011; 26: 3508-14).

A very important aspect of performing continuous elimination methods is their pharmacacoeconomics. The requirement is a safe and correctly indicated method associated with zero renal failure mortality, while the method must be financially viable. The method should be paid in full under the flat-rate payment per bed, which is the method of reimbursement in most countries with developed health systems. This means that the payment should fit the filter remuneration, the instrument set, the dialysis / substitution solution, anticoagulation and monitoring (Balik M, Zakharchenko M, January P, et al: Bioenergetic gain of citrate anticoagulated continuous haemodiafiltration - comparative study of two algorithms (J Crit Care 2011, under review). The current offer on the market makes it possible to enter a flat rate payment only for certain devices and with limited flow of company bags, corresponding to the already stable condition of the patient. With the need for increased dialysis or filtration flow, with or without citrate anticoagulation, it is possible to get off the flat rate payment for most devices and the method becomes financially loss-making.

The essence of the technical solution

The subject of the technical solution is a dialysis and substitution solution, especially for performing elimination methods in intensive care, in which citrate anticoagulation is applied. The essence of the invention is that the solution contains 125 to 135 mmol / l Na, 0 to 4 mmol / l K, 0.8 to 1.8 mmol / l Mg, 110 to 125 mmol / l Cl, 0.8 up to 1.2 mmol / l P, 15 to 25 mmol / l Na-lactate and 5.0 to 6.0 mmol / l glucose, the osmolality of this solution being in the range 270 to 285 mOsm / kg. In a preferred embodiment, the dialysis and substitution solution comprises 130 mmol / l Na, 2 mmol / l K, 1.5 mmol / l Mg, 116 mmol / l Cl, 1.0 mmol / l P, 18 mmol / l Na-lactate and 5.6 mmol / l glucose, the osmolality of this solution being 274 mOsm / kg.

The object of the invention is furthermore a single-chamber bag with a volume of 5000 ml universally usable with citrate anticoagulation, which contains the dialysis and substitution solution described above.

-4GB 23404 U1

Examples of technical solution

The essence of the solution is a new single-chamber bag, universally applicable with citrate anticoagulation, in unstable critically ill patients. The single-chamber bag has terminals allowing connection to various currently used devices (Fresenius Multifiltrate, Aqua5 rius Baxter, Braun Diapact, Kimal, and others). It has a volume of 5000 ml of a universal solution, allowing its use as a dialysis and haemofiltration solution for citrate anticoagulation.

It is intended to be used with 4% trisodium citrate. Its ionic composition and osmolality would not theoretically endanger the patient even in the case of human factor failure and accidental misuse with another, i.e. heparin anticoagulation.

The bag contains both dialysis and haemofiltration solutions for citrate anticoagulation, including 130 mmol / l Na, 2 mmol / l K, 1.5 mmol / l Mg, 116 mmol / l Cl, 1.0 mmol / l P, 18 mmol / l Lactate and 5.6 mmol / l glucose, the osmolality of this solution being in the region of 274 mOsm / kg. It has reduced sodium content, increased chloride content and reduced lactate buffer concentration. The reason is use with 4% trisodium citrate solution. Hypematremic citrate solution 15 carries the risk of elevating plasma sodium and alkalizing the patient with citrate (see above). In addition to the low sodium concentration, a reduced concentration of lactate buffer is used, where the anionic side of the solution replaces the buffer with chlorides.

The bag does not contain kale or um, as it would neutralize the citrate at the beginning of the blood set / filter and thus increase the necessary dose of citrate. Thus, the absence of calcium reduces the needed citrate dose at the beginning of the blood set, prolongs its survival and reduces the total systemic citrate dose to the patient (Package M, Zakharchenko M, January P, et al: Bioenergetic gain of anticoagulated citrate continuous haemodiafiltration - comparative study of two algorithms (J Crit Care 2011, under review).

Lack of evidence in favor of bicarbonate buffer, tested excellent tolerance of lac25 tate even in critical conditions (Pack M, Zakharchenko M, Otahal M, et al: Quantification of systemic dose of intermediate metabolism during citrate anticoagulation of continous renal replacement therapy. 2011), lactate buffer stability and its lower cost, sodium lactate buffer is chosen. The dose of lactate buffer is chosen rather at the lower desired value, as the blood pump flow can be increased when the pH drops, and the pH and 30 BE (base excess) upwards can be adjusted by the citrate dose. Once the patient has improved (many patients are attached to a severe CRRT associated with acidosis), the blood pump can be slowed down again and the citrate dose reduced. Low lactate levels should not lead to a significant increase in blood levels and arterial lactate may remain a marker of anaerobic metabolism. The systemic dose of lactate should be lower than that of 'classical' lactate buffer, expected to be about 30 to 40 mmol / h, a 35-day gain of about 750 to 1000 mmol of lactate, a dose metabolizable even in a circulatory unstable patient or severe hepatic insufficiency. Left B, Mansart A, Montemont C, et al: Myocardial lactate deprivation associated with deereased cardiovascular performance, deereased myocardial energy, and early death in endotoxic shock Intensive Care Med 2007, 33: 495502; Leverve X, Mustafa I. Novak I , et al: Lactate Metabolism in Acute Uremia. J Ren Nutr 40 2005, 15: 58-62). The stability of the lactate solution makes it possible to use a single-chamber bag, which further reduces its cost.

Unlike other solutions, the bag has a normal magnesia concentration value that significantly simplifies its monitoring and prevents the development of hypomagnesaemia on CRRT. The planned value should compensate for losses of 20 to 30 mmol per day (Zakharchenko M, Balik M, January P, et al: 45 Citrate anticoagulated continuous haemodiafiltration: Focus on ionised magnesium.

Care Med 2011, 37, S336 (abstract)) induced by both citrate anticoagulation and elimination without magnesium substitution. In addition, there is a normal phosphorus value preventing the phosphatemia from dropping to sometimes reported critically low patient-harmful values (Broman M, Carlsson O, Friberg H, Wieslander A, Godaly G:, Phosphate-containing dialysis solution causing hypo50 phosphatemia during continuous renal replacement therapy. Acta Anaesthesiol Scand 2011;

39-45; Demirjian S, Teo BW, Guzman JA, et al: Hypophosphatemia during continuous hemo

-5GB 23404 U1 dialysis is associated with prolonged respirators failure in patients with acute kidney injury. Nephrol Dial Transplant 2011; 26: 3508-14).

Standard glucose levels are commonplace as with other solutions. It is in the range allowing safe tight blood glucose control according to current recommendations (Van den Berghe G, Wilmer A, Hermans G, et al: Intensive insulin therapy in the medical ICU. N Engl J Med 2006, 354: 44961). In addition to calcium, a universal level of 2.0 mmol / l is chosen, which allows replenishment as needed and is also applicable in severe hyperkalemia.

The composition and stability of the solution makes it possible to use a single chamber bag with a predicted longer expiration time than bicarbonate buffered dual chamber bags. The use of a unicameral bag is associated with a lower production price, which should be reflected in the selling price close to that of current conventional lactate-buffered solutions on the market. With the use of polypropylene (a well-established GML system), there is no need for additional transport overpacks on the bags. The bag volume is a standard 5000 ml to be used on existing elimination methods whose weight system is calibrated to this weight.

The expected use in the filtrate / dialysate turnover is 20 to 35 ml / kg.h, i.e. 1500 to 4000 ml / h. The usual dose of the solution is between 1500 and 3000 ml / h with respect to evidence-based medicine from the CRRT area. Even with continuous venovenous haemofiltration (C WH) and division into 50% of the flow before and after replacement (i.e., administration before the filter) and 50% postdilution (i.e. administration after the filter), maintaining the filter fraction on the filter up to 20% would be sufficient 100 to 150 ml / min. This is sufficient and significantly higher blood flow than the current recommendations for the application of 4% citrate (80 to 110 ml / min, see Morger S, Haase M, Ruckert M, et al: Regional Citrate Anticoagulation in Continuous Hemodialysis - Acid-Base and Electrolyte Balance at Increased Dose of Dialysis, Nephron Clin Pract 2005, 101: 211-219; Morgera S, Schneider M; Slowinski T, et al: A safe citrate anticoagulation protocol with variable treatment efficacy and excellent control of acid-base status Crit Care Med 2009, 37: 2018-2024), allowing greater flexibility in patient ultrafiltration. As mentioned above, the dose of citrate before the filter is related to the flow through the blood pump. When using calcium-free bags, the expected consumption of 4% trisodium citrate is then between 170 and 220 ml / h. According to studies, this will lead to a systemic citrate dose of between 14 and 18 mmol / h (Package M, Zakharchenko M, January P, et al: Bioenergetic Gain of Citrate Anticoagulated Continuous Haemodiafiltration - Comparative Study of Two Algorithms. J Crit Care 2011, under review ). Estimated savings compared to bicarbonate buffered bags are (as of December 2011) approximately 80 to 100 CZK (3.3 to 4.2 EUR) per hour of operation, which is approximately 2100 CZK or 90 EUR / bedday. In the case of an average patient staying on a CRRT of about 7 to 14 days, it is already about 15 to 30,000 CZK or 630 to 1260 EUR / 1 patient. At present, there is no similar dialysis / substitution solution in the portfolio of companies in the world producing replacement solutions for elimination methods. This means an easy-to-manufacture, long-term stable, single-chamber and relatively inexpensive bag, universally applicable to citrate anticoagulation CRRT.

PROTECTION REQUIREMENTS

Claims (4)

Dialysis and substitution solution, in particular for performing elimination methods in intensive care, in which citrate anti-coagulation is applied, characterized in that it comprises 125 to 135 mmol / l Na, 0 to 4 mmol / l K, 0.8 to 1.8 mmol / l Mg, 110 to 125 mmol / l Cl, 0.8 to 1.8 mmol / l 1.2 mmol / l P, 15-25 mmol / l Na-lactate and 5.0-6.0 mmol / l glucose, the osmolality of this solution being in the range 270-285 mOsm / kg. Dialysis and substitution solution according to claim 1, characterized in that it comprises 130 mmol / l Na, 2 mmol / l K, 1.5 mmol / l Mg, 116 mmol / l Cl, 1.0 mmol / l P, 18 mmol / l Na-lactate and 5.6 mmol / l glucose, wherein the osmolality of the solution is 274 mOsm / kg. -6EN 23404 Ul A unicameral bag universally usable with citrate anticoagulant, characterized in that it comprises a disintegration and substitution solution according to claim 1 or 2. A unicameral bag according to claim 3 having a volume of 5000 ml.